SYSTEMS AND METHODS FOR DELIVERING PHARMACEUTICAL COMPOSITIONS TO THE NASAL CAVITY USING IONTOPHORESIS

20240207602

18/555935

April 12, 2022

Systems and methods for delivering pharmaceutical compositions to the nasal cavity using iontophoresis. The systems and methods include a delivery system that is disposed in operative apposition with a tissue surface, which delivery system can circulate iontophoretic solution having ions of a therapeutic substance in the nasal cavity. The circulation can be continuous or periodic. The circulation can replace the iontophoretic solution within the nasal cavity over a period of time, such as from 15 seconds to 1 minute. The systems and methods further include an electrode device that is utilized to apply current to perform the iontophoresis while the circulating of the iontophoretic solution in the nasal cavity. In some embodiments, the therapeutic substance is a steroid, and in further embodiments, the ions are betamethasone ions.

Smith & Nephew, Inc. (Memphis, TN, US), Smith & Nephew Orthopaedics AG (Zug, CH), Smith & Nephew Asia Pacific Pte. Limited (Singapore, SG)

1. A system comprising: (a) a reservoir structure operable for receiving an iontophoretic solution comprising ions of a therapeutic substance; (b) a delivery system comprising a delivery interface configured to be placed in operative apposition with a first side of a tissue surface within a nasal cavity of a subject, wherein (i) the delivery system is configured for circulating the iontophoretic solution to the reservoir structure over a predefined period of time; (c) an electrode device comprising a proximal portion and a distal portion, wherein (i) the electrode device configured for the proximal portion to be disposed outside of the nasal cavity while the distal portion extends into the nasal cavity into engagement with a portion of the reservoir structure, (ii) the electrode device further configured for applying a current to the reservoir structure such that an amount of the ions of the therapeutic substance is delivered to a target area of the subject on a second side of the tissue surface, (iii) the reservoir structure configured to maintain the delivery interface against the first side of the tissue surface for at least the predefined period of time during which current is being applied by the electrode device to the reservoir structure, and (iv) the circulating of the iontophoretic solution replenishes concentration of the ions of the therapeutic substance within the reservoir structure during the predefined period of time to enhance amounts of the therapeutic substance that are delivered to the target area.

2. The system of claim 1, wherein the delivery system is configured for circulating the iontophoretic solution having a continuous flow of iontophoretic solution.

3. The system of claim 1, wherein the delivery system is configured for circulating the iontophoretic solution having a periodic flow of iontophoretic solution.

4. The system of claim 1, wherein the delivery system is configured for circulating the iontophoretic solution at an average flow rate that replaces the iontophoretic solution in the reservoir structure in a period between 15 seconds and 1 minute.

5. The system of claim 1, wherein: (a) the delivery system is configured to provide for the iontophoretic solution to flow into the reservoir structure at or nearby the tissue surface; and (b) the delivery system is configured to provide for the iontophoretic solution to flow away from the reservoir structure at or nearby the distal portion of the electrode device.

6. The system of claim 1, wherein the electrode device is configured for applying the current utilizing a current profile having a ramp-up period, a steady state period, and a ramp-down period.

7. The system of claim 6, wherein the delivery system is configured for circulating the iontophoretic solution during the steady state period and for not circulating the iontophoretic solution during the ramp-up period and during the ramp-down period.

8. The system of claim 6, wherein (a) the delivery system is configured for circulating the iontophoretic solution during the ramp-up period at an average ramp-up period flowrate; (b) the delivery system is configured for circulating the iontophoretic solution during the steady state period at an average steady state period flow rate; and (c) the average steady state period flow rate is greater than the average ramp-up period flowrate.

9. The system of claim 1 further comprises a deployment device that is capable of being coupled and uncoupled to the delivery system, wherein the deployment device is operable for placing the delivery system within the nasal cavity.

10. The system of claim 1 further comprises a retrieval device that is capable of being coupled and uncoupled to the delivery system, wherein the retrieval device is operable for removing the delivery system from the nasal cavity.

11. The system of claim 1 further comprises a deployment/retrieval device that is capable of being coupled and uncoupled to the delivery system, wherein the deployment/retrieval device is operable for placing the delivery system within the nasal cavity and is further operable for removing the delivery system from the nasal cavity.

12. The system of claim 1, wherein the therapeutic substance is selected from a group consisting of analgesics, anesthetics, anti-inflammatoires, antibiotics, antivirals, antifungals, antiparasitics, decongestants, mucokinetics, antihistamines, antioxidants, immunosuppressive agents, dissociatives, steroids, sedatives, hypnotics, anticholinergics, antiemetics, antiepiletics, non-steroidal anti-inflammatory drugs, and combinations thereof.

13. The system of claim 1, wherein the therapeutic substance is a steroid.

14. The system of claim 1, wherein the iontophoretic solution comprises betamethasone ions.

15. The system of claim 1, wherein the therapeutic substance is an anesthetic.

16. The system of claim 1, wherein the iontophoretic solution comprises lidocaine ions, epinephrine ions, or a combination thereof.

17. A method comprising: (a) disposing a delivery system comprising a delivery interface in a nasal cavity of a subject such that the delivery interface is in operative apposition with a tissue surface; (b) utilizing the delivery system to circulate an iontophoretic solution comprising ions of a therapeutic substance into the nasal cavity; (c) while circulating the iontophoretic solution utilizing the delivery system, applying, during a predefined period of time and using an electrode device, a current to the delivery system such that a therapeutically effective dose of the therapeutic substance is delivered via the delivery interface to a target area below the tissue surface, wherein (i) the circulating of the iontophoretic solution replenishes concentration of the ions of the therapeutic substance within the nasal cavity during the predefined period of time to enhance amounts of the therapeutic substance that are delivered to the target area.

18. The method of claim 17, wherein the step of circulating the iontophoretic solution is a continuous flow of iontophoretic solution.

19. The method of claim 17, wherein the step of circulating the iontophoretic solution is a periodic flow of iontophoretic solution.

20. The method of claim 17, wherein the step of circulating the iontophoretic solution is at an average flow rate that replaces the iontophoretic solution in the nasal cavity in a period between 15 seconds and 1 minute.

21. The method of claim 17, wherein the step of circulating the iontophoretic solution comprises: (a) flowing the iontophoretic solution into the nasal cavity at or nearby the tissue surface; and (b) flowing the iontophoretic solution at or nearby the electrode device away from the nasal cavity.

22. The method of claim 17, wherein the step of applying the current to the delivery system comprises applying the current utilizing a current profile having a ramp-up period, a steady state period, and a ramp-down period.

23. The method of claim 22, wherein the step of circulating the iontophoretic solution comprises circulating the iontophoretic solution during the steady state period and not circulating the iontophoretic solution during the ramp-up period and during the ramp-down period.

24. The method of claim 22, wherein (a) the step of circulating the iontophoretic solution comprises circulating the iontophoretic solution during the ramp-up period at an average ramp-up period flowrate; (b) the step of circulating the iontophoretic solution comprises circulating the iontophoretic solution during the steady state period at an average steady state period flow rate; and (c) the average steady state period flow rate is greater than the average ramp-up period flowrate.

25. The method of claim 17 further comprising removing the delivery system from the nasal cavity.

26. The method of claim 25 further comprising performing a test to determine efficacy of the therapeutic substance delivered to the target area.

27. The method of claim 17, wherein the therapeutic substance is selected from a group consisting of analgesics, anesthetics, anti-inflammatoires, antibiotics, antivirals, antifungals, antiparasitics, decongestants, mucokinetics, antihistamines, antioxidants, immunosuppressive agents, dissociatives, steroids, sedatives, hypnotics, anticholinergics, antiemetics, antiepiletics, non-steroidal anti-inflammatory drugs, and combinations thereof.

28. The method of claim 17, wherein the therapeutic substance is a steroid.

29. The method of claim 17, wherein the iontophoretic solution comprises betamethasone ions.

30. The method of claim 17, wherein the therapeutic substance is an anesthetic.

31. The method of claim 17, wherein the iontophoretic solution comprises lidocaine ions, epinephrine ions, or a combination thereof.

32. A system comprising: (a) a reservoir structure operable for receiving an iontophoretic solution comprising ions of a therapeutic substance; (b) a delivery system comprising a delivery interface configured to be placed in operative apposition with a first side of a tissue surface within an interior region of a subject, wherein (i) the delivery system is configured for circulating the iontophoretic solution to the reservoir structure over a predefined period of time: (c) an electrode device comprising a proximal portion and a distal portion, wherein (i) the electrode device configured for the proximal portion to be disposed outside of the interior region while the distal portion extends into the interior region into engagement with a portion of the reservoir structure, (ii) the electrode device further configured for applying a current to the reservoir structure such that an amount of the ions of the therapeutic substance is delivered to a target area of the subject on a second side of the tissue surface, (iii) the reservoir structure configured to maintain the delivery interface against the first side of the tissue surface for at least the predefined period of time during which current is being applied by the electrode device to the reservoir structure, and (iv) the circulating of the iontophoretic solution replenishes concentration of the ions of the therapeutic substance within the reservoir structure during the predefined period of time to enhance amounts of the therapeutic substance that are delivered to the target area.

33. A method comprising: (a) disposing a delivery system comprising a delivery interface in an interior region of a subject such that the delivery interface is in operative apposition with a tissue surface; (b) utilizing the delivery system to circulate an iontophoretic solution comprising ions of a therapeutic substance into the interior region; (c) while circulating the iontophoretic solution utilizing the delivery system, applying, during a predefined period of time and using an electrode device, a current to the delivery system such that a therapeutically effective dose of the therapeutic substance is delivered via the delivery interface to a target area below the tissue surface, wherein (i) the circulating of the iontophoretic solution replenishes concentration of the ions of the therapeutic substance within the interior region during the predefined period of time to enhance amounts of the therapeutic substance that are delivered to the target area.

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edspap.20240207602